Table 2.

Major dimensions of biological heterogeneity in type 1 diabetes.

Dimension	Examples	Biological Impact	Therapeutic Implications	References
Age of onset	Pediatric vs. adult onset	Different immune activation intensity	Adjust immune-modulation strategies	(73, 75)
Genetic architecture	HLA-DR3/DR4, non-HLA loci	Alters antigen presentation	Precision immune therapies	(74, 113, 124)
Autoantibody patterns	GAD, IA-2, ZnT8	Predict progression rate	Stratified trial enrollment	(27, 75)
Immune phenotypes	T-cell dominant, interferon-high	Different inflammatory pathways	Targeted immunotherapies	(103, 123)
β-cell stress states	ER stress, oxidative stress	Increased immune recognition	β-cell protective therapies	(104, 131, 132)
Environmental factors	Microbiome, viral exposures	Immune priming	Preventive strategies	(35, 36, 110)